Protein kinase C regulation of GABA_A receptors

Abstract.

Pharmacological studies with drugs that activate or inhibit several protein kinase C (PKC) isozymes have identified the PKC family of serine-threonine kinases as important in the regulation of γ-aminobutyric acid type A (GABA_A) receptor function. PKC modulates GABA_A receptor surface density, chloride conductance and receptor sensitivity to positive allosteric modulators such as neurosteroids, ethanol, benzodiazepines and barbiturates. Recent studies using PKC isozyme-selective reagents and gene-targeted mice have begun to identify critical roles for three isozymes, PKCβII, PKCɛ and PKCγ, in various aspects of GABA_A receptor regulation. Progress in this field touches upon therapeutic areas that are of great clinical importance such as anxiety and addiction. Increased understanding of how PKC regulates GABA_A receptors and which PKC isozymes are involved holds promise for development of new treatments for diverse neuropsychiatric disorders.